The objectives of this project are to use laboratory animal (mouse) and a mouse tracheal organ culture model of cytomegalovirus (CMV) infections to examine some of the factors associated with natural or acquired resistance to CMV infections, to use the organ culture model to examine the biology and virology of persistent CMV infections and to analyze the differences between virulent and attenuated mouse cytomegalovirus. Some strains of mice are resistant to CMV both in vivo and in tracheal organ culture. Natural killer cell activity in infected mice and interferon levels in both mice and organ cultures will be examined. Isolated tracheal epithelial cells will be examined for resistance. Monoclonal antibodies against mouse CMV will be used to see if antigenic differences between virulent and attenuated viruses can be detected. These studies are designed to answer questions about resistance to CMV infections and possible modes of CMV persistence using murine CMV in animal and organ culture experimental systems. The determination of the ultimate mechanisms (or portions thereof) of CMV resistance and persistence in the mouse model might point the way to further studies in human beings to try to resolve basic questions concerning why some individuals are more adversely affected by CMV than are others.